- PRODUODOPA®
(foslevodopa/foscarbidopa) is the first-and-only subcutaneous
24-hour infusion of levodopa-based therapy for the treatment of
advanced Parkinson's disease
- PRODUODOPA demonstrated sustained
improvements in "Off" time (when symptoms return between medication
doses), "On" time (when symptoms are controlled) without dyskinesia
(involuntary movement), and morning akinesia ("Off" time upon
waking)
NORTH
CHICAGO, Ill., Jan. 9, 2024
/PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the launch
of PRODUODOPA® (foslevodopa/foscarbidopa) in the
European Union for the treatment of advanced Parkinson's disease
with severe motor fluctuations and hyperkinesia (excessive
movement) or dyskinesia (involuntary movement), and when available
combinations of Parkinson's medicinal products have not given
satisfactory results.1
PRODUODOPA is the first-and-only subcutaneous 24-hour infusion
of levodopa-based therapy for the treatment of severe motor
fluctuations in people living with advanced Parkinson's disease
whose symptoms are inadequately controlled by other therapies. The
continuous delivery of PRODUODOPA provides levodopa 24-hours a day
which may help patients by extending the period when symptoms are
well-controlled, often referred to as "On" time.2
AbbVie was granted marketing authorization of PRODUODOPA through
the Decentralized Procedure in the third quarter of
2022. The VYAFUSER™ pump for the subcutaneous delivery of
PRODUODOPA received Conformité Européenne (CE) Mark in November of
2023.
Parkinson's disease is a chronic, progressive neurodegenerative
disorder affecting approximately 6.1 million people
globally3 and is expected to double by 2040. Parkinson's
disease is characterized by tremor, muscle rigidity, slowness of
movement and difficulty with balance.4 As the disease
progresses, the severity of symptoms increases5, and
patients tend to experience greater disability and an impaired
ability to perform activities of daily living6, as well
as the reemergence of symptoms as standard treatment wears
off.7 Characteristics of advanced Parkinson's disease
may include needing help with performing daily activities,
increased motor fluctuations (changes in the ability to move
referred to as "On-Off" times), difficulty swallowing, recurrent
falls, dementia, dyskinesia (involuntary movements) and other
symptoms.5
"People living with Parkinson's disease experience daily
challenges and uncertainty, especially as their disease progresses
and symptoms are no longer adequately controlled," said
Roopal Thakkar, Senior Vice
President, Development and Regulatory Affairs and Chief Medical
Officer, AbbVie. "This approval is an example of our unwavering
commitment to this community by developing new, transformative
therapeutic options for people experiencing advanced Parkinson's
disease, their families, and care partners."
The launch was supported by three studies: the Phase 3, 12-month
open label study (M15-741 study) which evaluated the long-term
safety, tolerability, and efficacy of continuous subcutaneous
infusion of PRODUODOPA8, the Phase 3, 12-week study
(M15-736 study) which compared the efficacy and safety of
PRODUODOPA to oral levodopa/carbidopa2, and a Phase 1
pharmacokinetic comparability study.9
Findings from the M15-741 safety and tolerability study showed a
favorable benefit/risk profile and demonstrated sustained
improvements in "Off" time and "On" time without dyskinesia, and
morning akinesia as measured by the percentage of patients in early
morning "Off" time as recorded by PD diary.8
The majority of adverse events (AEs) with PRODUODOPA were
non-serious and mild or moderate in severity. The most frequent AEs
(greater than or equal to 10 percent) were infusion site events
(infusion site erythema, infusion site cellulitis, infusion site
nodule, infusion site pain, infusion site oedema, infusion site
reaction, and infusion site infection), hallucination, fall, and
anxiety.1
"This approval represents a significant advancement for those
with Parkinson's disease who have historically had limited
treatment options for advanced stages," said Angelo Antonini, MD, PhD, Professor of Neurology
at the Department of Neuroscience, University of Padua,
Italy. "When oral treatment no
longer sufficiently helps with improvement in motor fluctuations,
patients need alternative options. PRODUODOPA's around-the-clock
infusion allows for continuous delivery of levodopa, the gold
standard of treatment."
"As Parkinson's progresses, it can take a significant physical
and emotional toll not only on the person but also on their family
and care partners, who often play a critical role in their daily
lives," said Josefa Domingos,
President, Parkinson's Europe. "It
is vital that the Parkinson's community have more options that can
help them manage their symptoms."
About the Phase 3 M15-741 Study8
The Phase
3, single arm, open-label study evaluated the safety and
tolerability, and efficacy of 24-hour daily exposure of
continuous subcutaneous infusion of PRODUODOPA in people with
advanced Parkinson's disease whose motor symptoms were inadequately
controlled by their current treatment. The primary endpoint was to
evaluate the safety and tolerability of PRODUODOPA. Secondary
endpoints included changes from baseline in normalized "Off" and
"On" time, percentage of patients reporting morning akinesia, and
total scores from quality-of-life surveys. The study was conducted
at 58 sites across 13 countries (Australia, Belgium, Canada, Denmark, Germany, Italy, Japan,
Netherlands, Russia, Spain, Sweden, United
Kingdom, and United
States). Eligible patients included adults 30 years or older
diagnosed with levodopa-responsive idiopathic Parkinson's disease
experiencing an average of greater than or equal to 2.5 hours of
"Off" time per day, as assessed by patient's Parkinson's disease
diaries. Reduction in motor fluctuations was observed as early as
one week and persisted through week 52. The percentage of patients
experiencing morning akinesia dropped from 77.7 percent at baseline
to 27.8 percent at week 52. Indicators of sleep and quality of life
were assessed from baseline through week 52 as published in the
Journal of Neurology & Therapy
(https://doi.org/10.1007/s40120-023-00533-1). More information on
the study can be found on www.clinicaltrials.gov (NCT03781167).
About the Phase 3 M15-736 Study2
The Phase
3 randomized, double-blind, double-dummy, active-controlled study
compared the efficacy, safety and tolerability of PRODUODOPA to
oral immediate-release levodopa/carbidopa (LD/CD) in patients with
advanced Parkinson's disease. Participants were provided with a
home diary (the PD Diary) to assess their motor state during the
day. The primary endpoint was "On" time without troublesome
dyskinesia. The study included 141 participants who were randomly
assigned and received treatment at 65 centers in the U.S. and
Australia. Participants were
randomized one to one to receive either the PRODUODOPA solution as
a continuous delivery under the skin (subcutaneous) plus oral
placebo capsules for LD/CD or oral capsules containing
immediate-release LD/CD plus continuous subcutaneous delivery of
placebo solution for PRODUODOPA. The treatment duration was 12
weeks. The increase in "On" time without troublesome dyskinesia at
week 12 was an average of 2.72 hours for PRODUODOPA versus 0.97
hours for oral LD/CD (p= 0.0083). Improvements in "On" time were
observed as early as the first week and persisted throughout the 12
weeks. This study also assessed changes from baseline to week 12 in
motor experiences of daily living, morning akinesia, sleep, and
quality of life indicators, however results did not achieve
statistical significance. More information on the study can be
found on www.clinicaltrials.gov (NCT04380142) and in The Lancet
Neurology (https://doi.org/10.1016/S1474-4422(22)00400-8).
About the Phase 1 Pharmacokinetic study9
A
Phase 1, open label, randomized, two period cross over study was
conducted to compare the pharmacokinetics (PK) of levodopa from
24-hour continuous subcutaneous infusion of PRODUODOPA
(foslevodopa/foscarbidopa) to the PK of levodopa from 16-hour
levodopa-carbidopa intestinal gel (LCIG), followed by two
night-time oral levodopa/carbidopa (LD/CD) doses. The levodopa
exposures following subcutaneous infusion of PRODUODOPA over 24
hours were similar (less than 8 percent difference) to those of
LCIG mg LD/CD administered over 16 hours, followed by two oral
doses at 18 and 21 hours after the start of LCIG delivery. The
study concluded that 24-hour continuous subcutaneous infusion of
PRODUODOPA provides levodopa exposures comparable to LCIG
throughout the day. More information on the study can be found
on www.pubmed.ncbi.nlm.nih.gov (35339102) and in Science Direct
(https://doi.org/10.1016/j.parkreldis.2022.03.012).
About PRODUODOPA®
(foslevodopa/foscarbidopa)
PRODUODOPA®
(foslevodopa/foscarbidopa) is a solution of levodopa and carbidopa
prodrugs for 24-hour continuous subcutaneous infusion for the
treatment of advanced levodopa-responsive Parkinson's disease with
severe motor fluctuations and hyperkinesia or dyskinesia when
available combinations of Parkinson medicinal products have not
given satisfactory results.
PRODUODOPA® (foslevodopa and
foscarbidopa solution for infusion) Indication and Summary of
Important Treatment Considerations1
Indication
Treatment of advanced levodopa-responsive
Parkinson's disease with severe motor fluctuations and hyperkinesia
or dyskinesia when available combinations of Parkinson medicinal
products have not given satisfactory results.
Contraindications
PRODUODOPA is contraindicated in patients with hypersensitivity
to the active substances or to any of the excipients, narrow-angle
glaucoma, severe heart failure, acute stroke, severe cardiac
arrhythmia, co-medication with selective MAO type A inhibitors and
nonselective MAO inhibitors, conditions contraindicated for
adrenergics (e.g. pheochromocytoma, hyperthyroidism, and Cushing's
syndrome), and suspicious undiagnosed skin lesions or history of
melanoma.
Select special warnings and precautions for
PRODUODOPA
Special warnings and precautions for PRODUODOPA
Several warnings and precautions below are generic for levodopa
and, therefore, also for PRODUODOPA.
Not recommended for the treatment of drug-induced extrapyramidal
reactions.
Caution use in patients with: severe cardiovascular or pulmonary
disease, bronchial asthma, renal, hepatic or endocrine disease, or
history of peptic ulcer disease or of convulsions. History of
myocardial infarction with residual atrial nodal or ventricular
arrhythmias, cardiac function should be monitored during the
initial dosage adjustments. Monitor all patients for the
development of mental changes, depression with suicidal tendencies,
and other serious mental changes. Caution with past or current
psychosis and antipsychotics used concomitantly with dopamine
receptor-blocking properties (observe for loss of antiparkinsonian
effect). Higher frequency of hallucinations may occur with dopamine
agonists and/or other dopaminergic treatments including PRODUODOPA.
Monitor patients regularly for the development of impulse control
disorders, for example Dopamine Dysregulation Syndrome (DDS).
Before initiation of treatment, warn patients and caregivers of the
potential risk of developing DDS. The dose of PRODUODOPA may need
to be adjusted downwards in order to avoid levodopa induced
dyskinesias. Caution in chronic wide-angle glaucoma; monitor for
intra-ocular pressure changes. PRODUODOPA may induce orthostatic
hypotension and should be given cautiously in patients taking other
medicinal products that may cause orthostatic hypotension.
Concomitant use of selegiline and levodopa/carbidopa has been
associated with serious orthostatic hypotension. Levodopa may
induce somnolence and sudden sleep: caution should be exercised
when driving and operating machines. Risk of symptoms resembling
Neuroleptic Malignant Syndrome following abrupt dose reduction or
discontinuation.
Infusion site events (see section 4.8) have been reported in
patients receiving PRODUODOPA. Follow aseptic techniques and
frequently rotate the infusion site to reduce the risk. In clinical
studies, few patients who reported infusion site reactions also
experienced infusion site infections. Therefore, monitor for
serious infusion site reactions and infusion site infections.
Patients with Parkinson's disease have a higher risk of
developing melanoma. Monitor patients for melanomas on a
regular basis when using PRODUODOPA.
Periodic evaluation of hepatic, haematopoietic, cardiovascular
and renal function is recommended during extended therapy with
PRODUODOPA.
PRODUODOPA contains hydrazine (foscarbidopa degradation
product), that can be genotoxic and probably carcinogenic. The
approximately median exposure of hydrazine is 0.2 mg/day, with a
maximum of 0.5 mg/day. The clinical significance of this hydrazine
exposure is not known.
Reduced ability to handle the delivery system can lead to
complications. In such patients a caregiver should assist the
patient.
A sudden or gradual worsening of bradykinesia may indicate an
obstruction in the device for whatever reason and needs to be
explored.
Polyneuropathy has been reported; evaluate for history/signs of
and known risk factors before starting therapy.
PRODUODOPA is high in sodium; considered especially in patients
on a low salt diet.
Caution is needed in concomitant administration of PRODUODOPA
with the following medicinal products: Antihypertensives,
antidepressants, COMT inhibitors, dopamine antagonists, MAO
inhibitors, amantadine. Sympathomimetics may increase
cardiovascular adverse events related to
levodopa. Foscarbidopa is a potential inducer of CYP1A2 in
vitro. Care should be taken when prescribing PRODUODOPA in
combination with sensitive CYP1A2 substrates (e.g. caffeine).
Review section of interactions with other medicinal products in
SmPC for further details about these and a complete list of
interactions.
Fertility, pregnancy and lactation
PRODUODOPA is not recommended during pregnancy. Breast-feeding
should be discontinued during treatment with PRODUODOPA.
Undesirable effects
Summary of the safety profile
The most frequent adverse reactions (≥10%) reported in all Phase
3 studies in patients exposed to PRODUODOPA were infusion site
events (infusion site erythema, infusion site cellulitis, infusion
site nodule, infusion site pain, infusion site oedema, infusion
site reaction, and infusion site infection), hallucination, fall,
and anxiety.
This is not a complete summary of all safety information.
Globally, prescribing information varies; please refer to your
country specific product labeling for complete product prescribing
and safety information.
About AbbVie in Neuroscience
At AbbVie, our commitment
to preserving personhood of people around the world living
with neurological and psychiatric disorders is unwavering. With
more than three decades of experience in neuroscience, we are
providing meaningful treatment options today and advancing
innovation for the future. AbbVie's Neuroscience portfolio consists
of approved treatments in neurological conditions, including
migraine, movement disorders, and psychiatric disorders, along with
a robust pipeline of transformative therapies. We have made a
strong investment in research and are committed to building a
deeper understanding of neurological and psychiatric disorders.
Every challenge makes us more determined and drives us to discover
and deliver advancements for those impacted by these conditions,
their care partners, and clinicians. For more information, visit
www.abbvie.com.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines
and solutions that solve serious health issues today and address
the medical challenges of tomorrow. We strive to have a remarkable
impact on people's lives across several key therapeutic areas –
immunology, oncology, neuroscience, and eye care – and products and
services in our Allergan Aesthetics portfolio. For more information
about AbbVie, please visit us at www.abbvie.com.
Follow @AbbVie on X (formerly Twitter), Facebook, Instagram,
YouTube, and LinkedIn
Forward-Looking Statements
Some statements in this
news release are, or may be considered, forward-looking statements
for purposes of the Private Securities Litigation Reform Act of
1995. The words "believe," "expect," "anticipate," "project" and
similar expressions and uses of future or conditional verbs,
generally identify forward-looking statements. AbbVie cautions that
these forward-looking statements are subject to risks and
uncertainties that may cause actual results to differ materially
from those expressed or implied in the forward-looking statements.
Such risks and uncertainties include, but are not limited to,
challenges to intellectual property, competition from other
products, difficulties inherent in the research and development
process, adverse litigation or government action, and changes to
laws and regulations applicable to our industry. Additional
information about the economic, competitive, governmental,
technological and other factors that may affect AbbVie's operations
is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual
Report on Form 10-K, which has been filed with the Securities and
Exchange Commission, as updated by its subsequent Quarterly Reports
on Form 10-Q. AbbVie undertakes no obligation, and specifically
declines, to release publicly any revisions to forward-looking
statements as a result of subsequent events or developments, except
as required by law.
References
1 PRODUODOPA® (foslevodopa/foscarbidopa
solution for infusion) Summary of Product Characteristics.
November 2023.
2 Soileau, M., et al. Safety and efficacy of continuous
subcutaneous foslevodopa-foscarbidopa in patients with advanced
Parkinson's disease: a randomised, double-blind, active-controlled,
phase 3 trial. The Lancet Neurology. December 2022.
3 Armstrong, MJ. and
Okun, MS. (2020). Diagnosis and Treatment of Parkinson Disease. A
Review. JAMA 2020; 323(6): 548-560.
4 "What is Parkinson's?" Parkinson's Foundation.
Available at:
https://www.parkinson.org/understanding-parkinsons/what-is-parkinsons.
Accessed: August 29, 2023.
5 Luquin M-R et al. Parkinson's Dis. 2018; 4047392.
6 Malaty IA et al. (2022). Does the 5-2-1 criteria
identify patients with advanced Parkinson's disease? Real-world
screening accuracy and burden of 5-2-1-positive patients in 7
countries. Gainsville: BCM Neurology.
7 "Wearing off and motor fluctuations". Parkinson's
Europe. Available at
https://www.parkinsonseurope.org/about-parkinsons/symptoms/motor-symptoms/wearing-off-and-motor-fluctuations/#:~:text=Wearing%20off%20tends%20to%20happen,when%20medications%20will%20be%20effective.
Accessed November 6, 2023.
8 Aldred, J., et al. Continuous Subcutaneous
Foslevodopa/Foscarbidopa in Parkinson's Disease: Safety and
Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3
Study. Journal of Neurology & Therapy. August 2023.
9 Rosebraugh, M., et al. Foslevodopa/foscarbidopa
subcutaneous infusion maintains equivalent levodopa exposure to
levodopa-carbidopa intestinal gel delivered to the jejunum.
Science Direct. April 2022.
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